title: Mutation spectrum of primary hyperoxaluria type 1 in Tunisia: implication for diagnosis in North Africa.
abstract: BACKGROUND
  Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inherited metabolic disease, characterized by progressive kidney failure due to renal deposition of calcium oxalate. Mutations in the AGXT gene, encoding the liver-specific enzyme alanine glyoxylate aminotransferase, are responsible for the disease. We aimed to determine the mutational spectrum causing PH1 and to provide an accurate tool for diagnosis as well as for prenatal diagnosis in the affected families.
  
  
  METHODS
  Direct sequencing was used to detect mutations in the AGXT gene in DNA samples from 13 patients belonging to 12 Tunisian families.
  
  
  RESULTS
  Molecular analysis revealed five mutations causing PH1 in Tunisia. The mutations were identified along exons 1, 2, 4, 5 and 7. The most predominant mutations were the Maghrebian "p.I244T" and the Arabic "p.G190R". Furthermore, three other mutations characteristic of different ethnic groups were found in our study population. These results confirm the mutational heterogeneity related to PH1 in Tunisian population. All the mutations are in a homozygous state, reflecting the high impact of endogamy in our population.
  
  
  CONCLUSIONS
  Mutation analysis through DNA sequencing can provide a useful first line investigation for PH1. This identification could provide an accurate tool for prenatal diagnosis, genetic counseling and screen for potential presymptomatic individuals.
authors.affiliation: Institut Pasteur de Tunis, Laboratoire de Génomique Biomédicale et Oncogénétique, Tunis 1002, Tunisia.
authors.forename: Majdi
authors.initials: M
authors.lastname: Nagara
authors.forename: Afaf
authors.initials: A
authors.lastname: Tiar
authors.forename: Nizar
authors.initials: N
authors.lastname: Ben Halim
authors.forename: Faten
authors.initials: F
authors.lastname: Ben Rhouma
authors.forename: Olfa
authors.initials: O
authors.lastname: Messaoud
authors.forename: Yosra
authors.initials: Y
authors.lastname: Bouyacoub
authors.forename: Rym
authors.initials: R
authors.lastname: Kefi
authors.forename: Saida
authors.initials: S
authors.lastname: Hassayoun
authors.forename: Noura
authors.initials: N
authors.lastname: Zouari
authors.forename: Mohamed Slim
authors.initials: MS
authors.lastname: Ben Ammar
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
authors.forename: Jalel
authors.initials: J
authors.lastname: Chemli
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D006960:Hyperoxaluria, Primary / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D007223:Infant; D008297:Male; D025202:Molecular Diagnostic Techniques; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D000637:Transaminases / Q000235:genetics*; D014416:Tunisia; D055815:Young Adult
chemical_list: D000637:Transaminases; C019635:Alanine-glyoxylate transaminase
keywords: AGT; AGT-Mi; CaOx; Decisional tree; Diagnosis; ESRD; HGMD; Historical event; Human Gene Mutation Database; NC; Nephrocalcinosis; PH1; Primary hyperoxaluria; Primary hyperoxaluria type 1; SNPs; alanine glyoxylate aminotransferase; calcium oxalate; end-stage renal disease; minor allele haplotype; nephrocalcinosis; pyridoxine; single nucleotide polymorphisms; vitamin B6